WO2015030228A1

WO2015030228A1 - Porous plate for medical use and production method for porous plate for medical use

Info

Publication number: WO2015030228A1
Application number: PCT/JP2014/072877
Authority: WO
Inventors: 俊郎小泉; 長谷川　博; 浩志石幡; 直樹三木
Original assignee: 株式会社ラステック; 公立大学法人福島県立医科大学
Priority date: 2013-09-02
Filing date: 2014-09-01
Publication date: 2015-03-05
Also published as: JPWO2015030228A1; EP3042629B1; EP3042629A4; JP6082816B2; US20160183990A1; EP3042629A1; US10213239B2

Abstract

One embodiment of the present invention is a porous plate for medical use, having provided on a thin plate-shaped base material (61): a through-hole forming section (63) having a plurality of through-holes (62) formed therein; and a frame (64) surrounding the through-hole forming section. In this porous plate (60), the through-hole forming section (63) comprises: a crosspiece section (65) that is connected to the frame (64), extends in the front/rear and left/right directions, and partitions the through-hole forming section into a plurality of sections; and a plurality of through-hole forming cells (66) surrounded by the crosspiece section (65). The through-holes (62) formed in the through-hole forming cells (66) have a pore diameter of 1-50 µm, converted to a circular hole. The center-center distance between adjacent through-holes is 2-200 µm.

Description

Medical perforated plate and medical perforated plate manufacturing method

The present invention relates to a medical porous plate used as a medical auxiliary tool in the medical field such as living tissue regeneration and a method for manufacturing the same.

When a biological tissue is damaged by trauma, disease, or the like, if its damage is small, the form and function can be recovered by reconstructing a self-supporting tissue. However, when the scale of damage exceeds a certain level, it becomes difficult to restore the original form and function by restructuring a self-sustaining organization, and the sequelae of changes in form and function remain. For example, in a healthy state, the tooth root is supported stably by the surrounding alveolar bone in a healthy state, but when suffering from periodontal disease, the alveolar bone is destroyed by an inflammatory reaction, and the loss part is replaced with granulation tissue. Is done.

* Paragraph numbers are converted at the time of application As a means of recovering bone tissue lost due to disease, there is a guided tissue regeneration technique (GTR method), which is now widely used in dental clinics. Yes. In the GTR method, an isolation membrane is placed between the root of the alveolar bone near the alveolar bone that has been destroyed and absorbed by periodontitis and the gingival soft tissue frees the space for regenerating alveolar bone and induces regeneration from the remaining bone tissue. To do.

The isolation membrane used in the GTR method has a function to secure a regeneration space by separating the gingival soft tissue and the regeneration site of the alveolar bone for a predetermined period according to the growth of the bone tissue, and a function to prevent the tissue entry from the gingival soft tissue to the regeneration site. The function of permeating nutrients, physiologically active substances and the like from the gingival soft tissue rich in blood flow to the regenerated site of the alveolar bone is required. In other words, the separation membrane is required to have a filter function that allows nutrients and physiologically active substances to pass through while blocking (barriering) the passage of cells. Therefore, the isolation membrane used in such tissue regeneration medicine is called a barrier membrane.

Conventionally, barrier membranes made of polymer materials such as polytetrafluoroethylene (PTFE), polylactic acid, and polyurethane have been used. In addition, a porous barrier membrane made of sintered PTFE powder has been put to practical use, a barrier membrane made of non-woven polylactic acid, and a sponge-like matrix layer made of collagen and relatively impervious. A barrier membrane using a multilayer filter composed of a barrier layer is proposed (see, for example, Patent Document 1, Patent Document 2, Patent Document 3).

Two problems have been pointed out regarding the conventional barrier membrane as described above. The first problem is the thickness of the barrier membrane. Since the barrier membrane is embedded under the gingiva, it needs physical strength to maintain the membrane shape and maintain the regeneration space against the tissue pressure of the gingival soft tissue. In the case of a conventional barrier membrane made of a polymer material, the film thickness that satisfies this physical strength is about 200 to 400 μm. Since this thickness corresponds to several tens of cells, embedding a barrier membrane having such a thickness under the gingiva may reduce the space for regenerating periodontal tissue. The second problem is bacterial growth within the barrier membrane. The barrier membrane made of a polymer material has a porous sintered body or fiber form for achieving a filter function, and the matrix is rich in complicated and fine cavities. Although cells having a diameter of approximately 10 μm do not enter the microcavity, bacteria having a size of 1/10 or less can easily enter. Therefore, when oral bacteria enter the barrier membrane-buried part, the bacteria may propagate in a huge number of cavities, which are said to be several hundred million per square centimeter, and cause local infection.

In recent years, barrier membranes using metal thin plates as base materials have been proposed. For example, Patent Document 4 proposes a perforated plate in which a large number of through holes are formed in a thin metal plate by precision pressing using a micro perforation punch die. Further, Patent Document 5 proposes a support for osteoinductive regeneration in which a large number of through holes are formed in a metal thin plate by chemical etching using a photolithography technique.

JP-A-6-319794 JP 2002-325830 A JP 2009-61109 A JP 2011-142831 A JP 2011-212209 A

A perforated plate for regenerative medicine as disclosed in Patent Document 4 or 5 has been expected to be an effective means for solving the problems of conventional barrier membranes made of polymer materials. However, these perforated plates have the following problems.

The first problem is the problem of local bending and cracking that occurs with the deformation of the plate. When using a perforated plate as an isolation membrane, cut out the part where many through-holes are formed according to the treatment area with scissors, etc., and shape it so that it matches the shape of the affected area or surgical field where the plate is installed. It is used by fixing to the alveolar bone and jawbone with a pin or the like, or fixing to a dental crown or root using a suture thread or a wire. During the molding, the operator repeatedly performs complicated deformation so that the perforated plate has an appropriate shape. The perforated plate has a structure in which minute through holes are arranged in a thin plate at a high density. The arrangement of the through holes can be said to be a set of perforated rows, so it is easy to bend in the row direction, and if a local break occurs, it may be expanded by a relatively small force, and eventually the plate may be broken. was there.

The second problem is feasibility or productivity. When realizing the same function as a conventional barrier membrane made of a polymer material with a porous plate made of a metal material, it is necessary to form a large number of through-holes having a diameter of about 50 μm at intervals of about 60 to 200 μm in center distance. There is. It is extremely difficult to form such small diameter and high density through holes in a thin metal plate by punching. In addition, when through holes are formed in a thin metal plate at a high density by plastic processing, there is a problem that deformation after processing is significant due to the occurrence of residual stress, and for medical applications where stable physical properties are required. It is considered difficult to stably produce a perforated plate at a realistic production cost. The chemical etching process using the photolithography technique does not cause the above-described problems caused by the plastic processing. However, this processing method has a problem that uniform hole processing is difficult when the thickness of the metal material is increased, and there are problems that work is complicated and production efficiency is low because a large number of steps are required.

¡Because laser drilling is also performed in a non-contact manner, there is no problem caused by plastic working. However, laser processing for metal materials is basically thermal processing. Titanium, which is a typical example of the tissue regeneration base material, is a metal having extremely high reactivity with other elements at high temperatures, and titanium melted by thermal processing is instantaneously combined with oxygen to be vitrified. Since vitrified titanium loses its flexibility, if the vitrified region becomes large, brittle fracture is likely to occur. For this reason, it has been considered difficult to manufacture a medical porous plate by laser processing (see Patent Document 4).

The present invention has been made to solve the problems inherent to the perforated plate in which minute through holes are formed at a high density, and suppresses bending along the column direction, and temporarily breaks local breakage. An object of the present invention is to provide a medical perforated plate that can prevent expansion and breakage even if it occurs. Moreover, it aims at providing the production method of the porous plate which can produce such a porous plate stably.

1st aspect which illustrates this invention is a medical porous plate by which the thin-plate-shaped base material was provided with the through-hole formation part in which the several through-hole was formed, and the frame part surrounding a through-hole formation part. . In this perforated plate, the through-hole forming portion is configured to include a crosspiece that is connected to the frame portion, extends in the front-rear and left-right directions, and divides the through-hole formation portion into a plurality of pieces, and a plurality of through-hole forming cells surrounded by the crosspieces. Is done. The through hole formed in the through hole forming cell is configured such that the hole diameter converted to a circular hole is 1 to 50 μm, and the distance between the centers of adjacent through holes is 2 to 200 μm. Here, the hole diameter converted into a circular hole in this specification means the diameter when the shape of the through hole is a circle, and the shape of the through hole is a triangle, a quadrangle, a pentagon or more polygon, a star, etc. In this case, it means the diameter of a circle inscribed in these shapes.

The base material may be a biocompatible metal material having a plate thickness of 2 to 100 μm. Further, the size of the through-hole forming cell surrounded by the crosspiece can be configured such that the diameter of a circle inscribed in the cell is 0.5 to 5 mm. The width of the crosspiece can be set to 0.1 to 0.5 mm. Further, in addition to the through-holes, second through-holes having a diameter of 80 to 220 μm converted to circular holes can be formed dispersed in the through-hole forming cells at a center distance of 2 to 4 mm.

Further, the shape of the through-hole forming cells surrounded by the crosspieces is a regular polygon, and the through-hole forming cells can be formed to be uniformly distributed in the through-hole forming portions. In the present specification, a polygon means a plane figure surrounded by three or more sides, and a regular polygon means a polygon having the same length of each side. Alternatively, the shape of the through-hole forming cells surrounded by the crosspieces may be a hexagon having opposite sides parallel to each other, and the through-hole forming cells may be distributed and formed in a honeycomb shape in the through-hole forming portions. it can.

The second and third aspects exemplifying the present invention are methods for producing a medical porous plate. Prior to describing the configuration of the present invention in these aspects, the relationship between the pulse width of the laser light applied to the substrate and the thermal diffusion distance of the substrate will be described with reference to FIG. FIG. 1 is a graph showing the relationship between the pulse width of laser light irradiated on a base material and the diffusion distance (heat diffusion distance) of heat generated in the base material by laser light irradiation. It is calculated and plotted with respect to the material according to the theory of thermal diffusion.

In the thermal diffusion theory, the thermal diffusion distance δ is expressed as follows (laser ablation and its application, Institute of Electrical Engineers of Japan, published on November 25, 1999, Corona).
δ = (12κτ) ^1/2 (1)
Here, κ is the thermal diffusion coefficient of the base material, and τ is the pulse width of the laser light applied to the base material.

From the above equation (1), it is understood that the thermal diffusion distance δ increases as the pulse width τ of the laser light applied to the substrate increases, and the thermal diffusion distance δ increases as the thermal diffusion coefficient κ of the substrate increases. . Further, the expression (1) is a pulse for setting the thermal diffusion distance δ of heat generated by laser light irradiation to a desired value when the material of the base material used as the porous plate (that is, the thermal diffusion coefficient κ) is specified. This means that the width τ is obtained. The thermal diffusion distance represents an elementary process of heat propagation generated by irradiation with a single pulsed laser beam. Since drilling with a laser pulse is performed by irradiating a plurality of short pulses to the same spot, this elementary process of thermal diffusion is accumulated. As a result of the accumulation of the elementary processes, it is possible to envisage a temperature rise of the work material and accompanying alteration. For the above reasons, the thermal diffusion distance is an index for the thermal effect associated with pulse laser processing.

Figure 1 shows titanium (Ti), stainless steel (SUS), silver (Ag), magnesium (Mg), and alumina ceramics as an example from various materials used for medical purposes, and these materials are irradiated with laser light. The results of calculating the relationship between the pulse width τ and the thermal diffusion distance δ are plotted. At this time, the value of 300 K, which is room temperature, was used as the thermal diffusion coefficient κ. From FIG. 1, for example, when the base material is alumina ceramics, in order to set the thermal diffusion distance to 3 μm, the pulse width of the laser beam may be set to about 60 nsec (nanoseconds), and the thermal diffusion distance is suppressed to 2 μm or less. In order to do so, it is understood that the pulse width of the laser light needs to be set to about 30 nsec or less.

A second aspect exemplifying the present invention is a method for producing a medical porous plate in which a thin plate-like base material is irradiated with laser light to form a plurality of through holes in a through hole forming part surrounded by a frame part. is there. The manufacturing method of this aspect has a pulse width determined based on the thermal diffusion distance in the base material, leaving a crosspiece that extends in the front-rear and right-left directions and divides the through-hole forming part into a plurality of parts, in the through-hole forming part. Irradiate laser light to form a through hole with a hole diameter of 1 to 50 μm converted to a circular hole and a distance between the centers of adjacent through holes of 2 to 200 μm. The through hole forming part is surrounded by a crosspiece. And forming a plurality of through-hole forming cells in which a plurality of through-holes are formed.

The base material may be a biocompatible metal material having a plate thickness of 2 to 100 μm. The thermal diffusion distance can be 1 μm or less. The pulse width may be 10 nsec or less.

In a third embodiment illustrating the present invention, a thin plate-like substrate made of titanium or a titanium alloy having a thickness of 2 to 100 μm is irradiated with laser light, and a plurality of through-hole forming portions surrounded by a frame portion are irradiated with a plurality of holes. It is a manufacturing method of the medical porous plate which forms a through-hole. In the manufacturing method of this aspect, the through hole forming portion is irradiated with laser light having a pulse width of 10 nsec or less, leaving a crosspiece that is connected to the frame portion and extends in the front, rear, left, and right to partition the through hole forming portion into a plurality of holes. The diameter of the converted hole is 1 to 50 μm, and the distance between the centers of adjacent through holes is 2 to 200 μm. A plurality of through holes are formed in the through hole forming portion surrounded by the crosspieces. It is configured by forming a plurality of through-hole forming cells.

In the method for manufacturing the medical porous plate of the second aspect and the third aspect, the size of the through hole forming cell surrounded by the crosspiece is such that the diameter of a circle inscribed in the cell is 0.5 to It can be configured to be 5 mm. The width of the crosspiece can be set to 0.1 to 0.5 mm. Further, in addition to the through-holes, second through-holes having a diameter of 80 to 220 μm converted to circular holes can be formed dispersed in the through-hole forming cells at a center distance of 2 to 4 mm.

Further, the shape of the through-hole forming cells surrounded by the crosspieces is a regular polygon, and the through-hole forming cells can be formed to be uniformly distributed in the through-hole forming portions. Alternatively, the shape of the through-hole forming cells surrounded by the crosspieces may be a hexagon having opposite sides parallel to each other, and the through-hole forming cells may be distributed and formed in a honeycomb shape in the through-hole forming portions. it can.

In the perforated plate for medical use according to the first aspect, the through-hole forming portion is connected to the frame portion and extends in the front-rear and left-right directions to partition the through-hole forming portion into a plurality of through-holes surrounded by the cross-piece portion. Cell. That is, the through-hole forming part is formed by a plurality of through-hole forming cells in which many fine through holes are formed surrounded by the crosspieces. For this reason, a line connecting adjacent through holes sequentially is divided by the crosspieces, and a certain elasticity is maintained, and bending of the perforated plate along the arrangement direction of the through holes is suppressed. In addition, the presence of the crosspiece prevents the progress of cracking and tearing.

In addition, by configuring the size of the through-hole forming cell surrounded by the crosspieces so that the diameter of a circle inscribed in the cell is 0.5 to 5 mm, a sufficient number of through-holes for tissue regenerative medicine A large number of crosspieces can coexist with each through-hole forming cell. As a result, even if a local breakage occurs, the breakage stops at the crosspiece and does not reach the adjacent through-hole forming cell, so the breakage can be suppressed to a minute range, and the plate breaks. Can be prevented. By setting the width of the crosspiece portion to 0.1 to 0.5 mm, it is possible to give an appropriate elasticity, and it is possible to securely fix the porous plate by placing fixing pins on the crosspiece portion. .

Further, in addition to the through holes formed in the through hole forming cell, second through holes having a hole diameter converted to a circular hole of 80 to 220 μm are dispersed and formed in the through hole forming cell with a center distance of 2 to 4 mm. According to such a configuration, for example, cells that can generate reticulated blood vessels as host-derived cells enter the depletion region secured by the second through-hole, so that nutrients by blood flow can be introduced into the transplanted cultured cell sheet. It is expected that a supply channel will be formed. In addition, a fixing pin can be driven using the second through hole, and a medical porous plate having both functions and convenience can be provided.

In addition, the shape of the through-hole forming cell surrounded by the crosspieces is a regular polygon, and the configuration in which the through-hole forming cells are uniformly distributed in the through-hole forming portion and the shape of the through-hole forming cell are According to the configuration in which the opposite sides are parallel hexagons, and the through-hole forming cells are distributed and formed in the through-hole forming portion in a honeycomb shape, the bending and crack progress in a certain direction along the arrangement of the through-holes. In addition, the strength can be made uniform because it can be arranged isotropically with a constant crosspiece width, and substantially uniform elasticity can be given to bending in an arbitrary direction.

As described above, the medical porous plate according to the first aspect is useful as a medical porous plate that solves the problems peculiar to porous plates in which minute through holes are formed at high density.

In the manufacturing method of the medical porous plate of the second and third aspects, the through hole is formed by irradiating a laser beam having a pulse width determined based on a thermal diffusion distance in the base material when the laser beam is irradiated. Is done. Therefore, according to these manufacturing methods, it is possible to provide a perforated plate that is substantially free from thermal influence. In addition, in this manufacturing method, each through hole is sequentially formed by irradiating the base material with a pulsed laser beam, so that it is possible to stably produce a porous plate having fine through holes formed at a high density. Can do.

In the method for manufacturing the medical porous plate according to the second and third aspects, the laser is left in the through hole forming portion, which is connected to the surrounding frame portion and extends in the front / rear and left / right directions to partition the through hole forming portion into a plurality of portions. Irradiated with light, a plurality of through-hole forming cells in which a plurality of through-holes are formed surrounded by a crosspiece are formed, and a medical porous plate is manufactured. The medical porous plate manufactured in this way has a through-hole forming portion formed by a plurality of through-hole forming cells surrounded by a crosspiece and formed with many fine through-holes. Therefore, a line connecting adjacent through holes sequentially is divided by the crosspieces, and a certain elasticity is maintained, and bending of the perforated plate along the arrangement direction of the through holes is suppressed. Moreover, durability with respect to bending of a raw material can be improved by presence of a crosspiece.

In addition, by setting the thermal diffusion distance that defines the pulse width to 1 μm or less, it is possible to provide a porous plate that is hardly affected by the laser beam irradiation. In addition, by setting the pulse width of the laser beam to be irradiated to 10 nsec or less, a porous plate is provided so that the thermal effect does not cause any problems in use for many materials used in tissue regeneration medicine such as titanium and alumina ceramics. can do.

In addition, the shape of the through-hole forming cell surrounded by the crosspieces is a regular polygon, and the configuration in which the through-hole forming cells are uniformly distributed in the through-hole forming portion and the shape of the through-hole forming cell are According to the configuration in which the opposite sides are parallel hexagons, and the through-hole forming cells are distributed in a honeycomb shape in the through-hole forming portion, the bending and crack progress in a certain direction along the through-hole arrangement. In addition, the strength can be made uniform because it can be arranged isotropically with a constant crosspiece width, and substantially uniform elasticity can be given to bending in an arbitrary direction. In addition, by setting the width of the crosspiece to 0.1 to 0.5 mm, an effect of partitioning the cell group adhering to the through-hole forming part in a block shape is expected. It becomes possible to show an effect and to give a pharmacological action. Or the nutrient supply and chemical | medical agent which can use the crosspiece as a passage can be performed. In addition, for cells with excellent extensibility such as fibroblasts, when migrating on a plate and progressing, a cell pseudopod that crosses the crosspieces so as to cross between the perforated areas divided by the crosspieces Can be produced.

Therefore, according to the manufacturing method of the medical porous plate as described above, it is possible to manufacture a medical porous plate that solves the problems inherent to the porous plate in which minute through holes are formed at high density.

In the above description, the GTR method is exemplified as an example of tissue regeneration medicine. However, tissue regeneration induction using the porous plate of the present invention may be performed by a bone regeneration induction method (GBR method: Guided Bone Regeneration technique) or various organs. Although it has a certain level of regeneration ability, such as the tissue regeneration induction method, the growth rate is inferior to that of the surrounding tissue, so that it can be applied to various tissue regenerations that prevent self-sustaining recovery.

In the medical porous plate manufactured and configured as described above, the through hole formed in the base material can be configured such that the hole diameter converted to a circular hole is 1 to 20 μm. The size of the opening through which normal human tissue cells can pass is said to have a minimum diameter of about 10 μm. In practice, however, the passage of cells is considerably restricted even if the through-hole is larger than that. For example, in a perforated plate in which a large number of through-holes having a pore diameter of 20 μm were formed, it was experimentally confirmed that a large number of cells adhered and proliferated on the plate surface, and the number of cells permeated through the through-holes was considerably small. Therefore, by setting the diameter of the through hole to 1 to 20 μm, a barrier function for preventing tissue entry can be sufficiently achieved. Further, if the through hole has a diameter of 1 to 10 μm, a substantially complete cell barrier can be achieved.

It is a graph which shows the relationship between the pulse width of the laser beam irradiated to a base material, and the diffusion distance (heat diffusion distance) of the heat | fever which generate | occur | produced in the base material by irradiation of a laser beam. It is a schematic block diagram of the laser processing system shown as an example of an apparatus suitable for producing a perforated plate. It is a block block diagram of the said laser processing system. It is explanatory drawing for demonstrating the area | region which forms a through-hole in a to-be-processed material. It is a schematic diagram of the medical porous plate illustrated as an example of the medical porous plate to which this invention is applied. It is explanatory drawing for demonstrating the effect | action of a medical porous plate. It is a schematic diagram which illustrates the shape of the through-hole formed in a medical porous plate. It is a schematic diagram which shows the structural example of the medical porous plate which formed the 2nd through-hole in the through-hole formation cell. It is a schematic diagram which shows the other structural example of a through-hole formation part. It is a schematic diagram of the structural example which formed the 3rd through-hole for fixing pin placement which fixes a medical porous plate in the crosspiece. It is an external view (whole observation image) of the medical porous plate shown as an example of the porous plate produced by the production method of the present invention. It is the elements on larger scale (magnification observation image) of the example of composition of the penetration hole formation part in the medical porous plate shown in FIG. FIG. 13 is a partial enlarged view (transmission enlarged observation image) showing a formation state of through holes formed in the through hole forming cell of the through hole forming portion shown in FIG. 12. FIG. 12 is a partially enlarged view (an enlarged observation image) of another configuration example of the through hole forming portion in the medical porous plate shown in FIG. 11. It is the elements on larger scale (transmission enlarged observation image) which shows the formation state of the through-hole formed in the through-hole formation cell of the through-hole formation part shown in FIG. It is the (a) external view of a perforated plate and (b) the elements on larger scale of a through-hole formation part shown as other structural examples of the perforated plate produced with the manufacturing method of this invention. It is the (a) external view of a perforated plate and (b) the elements on larger scale of a through-hole formation part shown as other structural examples of the perforated plate produced with the manufacturing method of this invention. It is the elements on larger scale (magnification observation image) of the medical porous plate which showed the smaller diameter through-hole formed as still another structural example of the porous plate produced by the manufacturing method of the present invention. It is a table | surface of the experimental result which performed the hole process by changing the conditions of the laser beam irradiated to a base material, and investigated the heat affected zone (HAZ). It is an example of the experimental result which verified the effect of the cell adhesion in a medical porous plate. It is an example (comparison example) of the experimental result which verified the effect of the cell adhesion in a medical porous plate.

Hereinafter, modes for carrying out the present invention will be described. As an example of a suitable apparatus used in the method for producing a medical porous plate according to the present invention, a schematic configuration of a laser processing system is shown in FIG. 2, and a block configuration diagram thereof is shown in FIG. First, an outline of the laser processing system will be described with reference to these drawings. In FIG. 2, what is indicated by a two-dot chain line is an electrical signal line such as a control cable.

The laser processing system LS includes a laser device 10 that outputs a laser beam Lb, a stage 30 that holds a workpiece W that is a material of a perforated plate, and moves the workpiece W in two directions that are orthogonal to each other in a horizontal plane. The beam scanner 20 and the fθ lens 25 provided on the optical path for guiding the laser beam Lb output from the laser device 10 to the workpiece W held on the stage 30, the laser device 10, the beam scanner 20, the stage 30, and the like And a control device 50 for controlling the operation of the apparatus.

The laser device 10 is configured to be capable of outputting a short pulse laser beam Lb having a pulse width of 300 fsec to 100 nsec and an average power of about 100 mW to 5 W. The wavelength of the laser beam output from the laser device 10 can be selected from an infrared region having a wavelength of about 1 μm to an ultraviolet region having a wavelength of about 300 nm.

In addition to the beam scanner 20, the laser beam Lb output from the laser device 10 is collimated into parallel light in the optical system that guides the laser beam Lb output from the laser device 10 to the workpiece W held on the stage 30. A collimator 26 and a light guide optical element (not shown) for guiding the laser light emitted from the collimator 26 to the beam scanner 20 are provided. Note that a beam expander that adjusts the beam diameter of laser light, a polarizing optical element that adjusts the polarization state, and the like may be provided.

The beam scanner 20 is a scanner device that scans the workpiece W held on the stage 30 with a laser beam. In this configuration example, the scanner device that scans the laser beam in the XY direction using a galvanometer mirror. (Galbano scanner) is illustrated. That is, the beam scanner 20 mainly includes an X galvanometer mirror 21 that scans the workpiece W in the X direction and a Y galvanometer mirror 22 that scans the workpiece W in the Y direction. Composed. A driver for driving the X galvanometer mirror 21 and the Y galvanometer mirror 22 is provided in the control device 50.

The fθ lens 25 is a lens that condenses the laser beam deflected by the beam scanner 20 on the surface (image plane) of the flat workpiece W, converts the equiangular motion of the scanner into a constant velocity motion, and scans it. . In the laser processing system LS, a telecentric type fθ lens that condenses and enters the laser beam deflected by the beam scanner 20 and incident on the fθ lens 25 vertically onto the surface of the workpiece W is used. Thereby, the through-hole formed in a base material becomes a perpendicular | vertical and uniform diameter to the base-material surface irrespective of a processing position, and many through-holes can be formed with high position accuracy.

The stage 30 includes a chuck 35 that fixes and holds the workpiece W horizontally, an X stage 31 that moves the workpiece W held on the chuck 35 in the X direction, a Y stage 32 that moves the workpiece W in the Y direction, and the like. Composed. A Z stage that moves the workpiece W held by the chuck 35 in the Z direction (vertical direction) orthogonal to the horizontal XY plane, and a θ stage that rotates the chuck 35 around the Z axis extending in the vertical direction. Etc. may be provided.

The control device 50 includes an oscillation control unit 51 that controls the operation of the laser device 10, a scanner control unit 52 that controls the operation of the beam scanner 20, a stage control unit 53 that controls the operation of the stage 30, and a control program set and stored in advance. Or a controller 55 that outputs a command signal to each of the

control units

51, 52, 53 based on the read machining program.

The oscillation control unit 51 controls the operation of the laser device 10 based on the command signal output from the controller 55. Specifically, the oscillation control unit 51 causes the laser device 10 to generate laser light having a peak power, a pulse width, and a pulse period corresponding to the pulse command signal output from the controller 55, and turn on / off according to the output command signal. The laser device 10 outputs the signal at the off timing.

The scanner control unit 52 controls the operation of the beam scanner 20 based on the command signal output from the controller 55. Specifically, the scanner control unit 52 controls the driving of the X galvano mirror 21 and the Y galvano mirror 22 in accordance with the scanning command signal output from the controller 55, and the position, scanning speed, A laser beam is focused and irradiated on the workpiece along the scanning locus. For example, when a through hole having a hole diameter close to the focused spot diameter is formed at a predetermined position of the workpiece W, the scanner control unit 52 causes the X galvanoscope so that the irradiation position of the laser beam becomes the predetermined position. The angular positions of the mirror 21 and the Y galvanometer mirror 22 are controlled. In addition, when a through-hole having a square shape or a star shape is formed on the basis of a predetermined position, the laser beam is scanned at a predetermined scanning speed with a predetermined scanning speed on the basis of the predetermined position. The drive of the X galvanometer mirror 21 and the Y galvanometer mirror 22 is controlled so as to move along the locus.

The stage control unit 53 controls the operation of the stage 30 based on the command signal output from the controller 55. Specifically, the stage control unit 53 drives the X stage 31 and the Y stage 32 in accordance with the position command signal output from the controller 55, and moves the workpiece W held on the chuck 35 to a predetermined position. . For example, when the drilling of a region that can be processed by beam scanning by the beam scanner 20 (referred to as a scanning processing region) is completed, the stage control unit 53 determines the position corresponding to the position command signal output from the controller 55, that is, the next The workpiece W is moved to a position to be a scanning machining area and held at that position.

The controller 55 is configured on the basis of a personal computer, and is used to input and change various information including a display device that displays various information such as operating conditions and setting conditions of each unit, a selected machining program, and machining position information. For example, a keyboard for reading a machining program and CAD data, a mouse for selecting machining conditions, and the like.

Therefore, according to the laser processing system LS schematically configured as described above, the processing program is read by the controller 55, and various setting conditions are selected or corrected as necessary, and laser processing is started. Thereby, the laser beam having the pulse condition set in the machining program is focused and irradiated at the position set in the machining program, and the through hole having the shape set in the machining program can be formed.

Next, a manufacturing method of a medical porous plate using the laser processing system LS will be described. An example of a method for producing a perforated plate is to irradiate a workpiece W with a laser beam having a pulse width determined based on a thermal diffusion distance in the workpiece when the workpiece is irradiated with a laser beam. Are formed so as to sequentially form through holes in which the distance between the centers of adjacent through holes is 2 μm to 200 μm.

Here, the workpiece W that forms the base material of the porous plate is a thin plate, that is, a material that is not a porous or fibrous material but a dense solid and has high biocompatibility. Examples of such materials include a thin plate made of a metal material such as titanium, a titanium alloy, and a silver alloy, a thin plate made of an inorganic material such as alumina ceramics, or a thin plate made of a polymer material such as PTFE or polylactic acid. The

Polymer materials such as PTFE and polylactic acid are materials that have already been used in many ways in tissue regeneration medicine for alveolar bone by the GTR method. When such a thin plate-like material made of a polymer material is used as the workpiece W, that is, the base material of the porous plate, the same as in the conventional barrier membrane of the same material (for example, PTFE) The thickness for imparting physical strength can be reduced.

When a metal material having biocompatibility is used as the base material (workpiece W) of the perforated plate, the plate thickness can be set to 2 to 100 μm while maintaining the strength and elasticity of the base material. Further, the thickness can be further reduced as compared with the porous plate made of a polymer material. In addition, it is possible to produce a porous plate that is more flexible and easy to handle than when an inorganic material such as alumina ceramic is used.

Various metal materials such as titanium, titanium alloy, stainless steel, cobalt-chromium alloy, cobalt-chromium-molybdenum alloy, tantalum, zirconium, gold, platinum, and silver alloy can be used as biocompatible metal materials. However, in particular, as described above, titanium or a titanium alloy is widely used as a metal material having biocompatibility in both medical and dental fields, and has many medical achievements. Therefore, by using a plate made of titanium or a titanium alloy as the base material of the porous plate, a porous plate that can be widely applied in the tissue regeneration medical field can be produced.

In the illustrated method for producing a perforated plate, laser light having a pulse width determined based on the thermal diffusion distance in the work material when the work material W that is the base material of the perforated plate is irradiated with laser light is condensed and irradiated. By doing so, a through hole is formed. Here, the pulse width of the laser light determined based on the thermal diffusion distance in the substrate is obtained by the thermal diffusion theory as described with reference to the equation (1) and FIG. 1, and the material of the workpiece W is determined as follows. If it is known, the pulse width for setting the thermal diffusion distance to a desired value can be obtained. Referring to FIG. 1 again, for example, when the material of the workpiece W is titanium, in order to reduce the diffusion distance of heat absorbed by the workpiece by the laser beam irradiation to 1 μm or less, the pulse of the laser beam to be irradiated It can be seen that the width should be 10 nsec or less.

At this time, the aspect of the thermal influence generated on the workpiece W due to the absorption of heat and the thickness thereof vary depending on the material of the base material. However, if the thermal diffusion distance is 1 μm or less, it is possible to produce a perforated plate in which the thermal effect does not cause a problem in use. In addition, since each through hole is sequentially formed by irradiating the workpiece W with a pulsed laser beam, it is possible to stably provide a perforated plate in which fine through holes are formed at a high density. . The condition of the laser beam output from the laser device 10 is set by the controller 55, and the laser beam having the set pulse width, repetition period, and peak power is output from the laser device 10 and focused on the workpiece W. The

The size of the through hole to be drilled in the workpiece W can be set to an appropriate hole diameter in the range of 1 to 50 μm in hole diameter converted to a circular hole. At this time, when the hole diameter of the through hole to be drilled is close to the condensing spot size (for example, when the hole diameter of the through hole is about φ1 to 20 μm), the condensing position of the laser beam irradiated to the workpiece W ( The focal position is set to a height position corresponding to the hole diameter, and the X galvanometer mirror 21 and the Y galvanometer mirror 22 are fixed at the position where the through hole is to be formed, and the laser beam can be set to be irradiated. On the other hand, when the diameter of the through-hole to be drilled is larger than the focused spot size (for example, when the diameter of the through-hole is about φ10 to 50 μm), the focal position of the laser beam irradiated to the workpiece W Is set to be the surface or inside of the workpiece W, and the X galvanometer mirror 21 and the Y galvanometer mirror 22 are driven so that the laser beam moves along a movement locus corresponding to the hole diameter.

The distance between the centers of adjacent through holes can be set to an appropriate pitch in the range of 2 to 200 μm. Specifically, in a scanning processing region that can be processed by beam scanning by the beam scanner 20, a plurality of through holes are formed at predetermined positions by controlling the angular positions of the X galvanometer mirror 21 and the Y galvanometer mirror 22. Thus, adjacent through holes can be formed at a predetermined pitch. Further, when the hole machining in the scanning machining area is completed, the workpiece W held by the chuck 35 by driving the X stage 31 and / or the Y stage 32 of the stage 30 is set to a position that becomes the next scanning machining area. A plurality of through holes are formed at predetermined positions by beam scanning by the beam scanner 20 at the position. Thereby, a through-hole can be formed in a predetermined pitch in a wide range. The controller 55 can also set conditions regarding these through holes.

The controller 55 outputs a command signal to the oscillation control unit 51, the scanner control unit 52, and the stage control unit 53 based on a control program that has been set and stored in advance and a machining program that has been read, and the laser device 10, the beam scanner 20, and By controlling the operation of the stage 30, through holes are sequentially formed in the position region set by the machining program.

Here, the through-hole formation region set in the machining program is not the entire region of the workpiece W, but a central region Af (with a frame portion of a predetermined width left in the periphery as shown by a two-dot chain line in FIG. It is a through-hole formation part 63). Further, in the perforated plate according to the present invention, instead of forming a through hole in the entire through hole formation region Af surrounded by the two-dot chain line, leaving a crosspiece that is connected to the peripheral frame portion and extends in the front-rear and left-right directions, Through holes are formed in the divided areas partitioned by the crosspieces.

FIG. 5 shows a schematic diagram of a porous plate 60 in which a large number of through holes are formed in the through hole forming region Af as an example of the porous plate manufactured by the manufacturing method as described above. The perforated plate 60 includes a thin plate-like base material 61 (workpiece W) having a through hole forming portion 63 in which a large number of through holes 62 are formed and a frame portion 64 surrounding the through hole forming portion. Is done. The through-hole forming portion 63 is provided with a crosspiece 65 that is connected to the frame portion 64 and extends in the front-rear and left-right directions to partition the through-hole forming portion 63 into a plurality of parts. The holes 62 are sequentially formed to form a plurality of through-hole forming cells 66 including a group of through-

holes

62, 62, 62.

FIG. 5 shows a configuration example in which the shape of the through-hole forming cell 66 surrounded by the crosspiece 65 is a regular hexagon, and the through-hole forming cell 66 is formed in the through-hole forming portion 63 with a honeycomb-like distribution pattern. The size and arrangement of the through holes 62 formed in each through hole forming cell 66 are such that the hole diameter converted to a circular hole is 1 to 50 μm, and the distance between the centers of the adjacent through

holes

62 and 62 is 2 to 200 μm. Is set. For example, the hole diameter is 1 μm, the center distance is 2 μm, the hole diameter is 10 μm, the center distance is 50 μm, the hole diameter is 20 μm, the center distance is 100 μm, the hole diameter is 50 μm, and the center distance is 200 μm. The distance between the centers of the adjacent through

holes

62 and 62 can be appropriately set within a range of 2 to 200 μm on condition that the through holes are not connected to each other (each is an independent through hole). In addition, if it is set as the range in which the thermal diffusion distance of each through-hole does not overlap, a high-density porous plate can be obtained while suppressing tissue transformation or deformation that may be caused by heat.

Here, when the hole diameter of the through-hole 62 is set in the range of 30 to 50 μm, the cell passage inhibitory effect equivalent to the conventionally used barrier membrane made of a sintered or fibrous polymer material is obtained. be able to. On the other hand, the perforated plate 60 of this configuration has a simple perforated filter structure in which a hole having the above-mentioned hole diameter is formed through a thin plate-like base material 61 so that it can be made thinner than a conventional barrier membrane. In addition, local infections caused by bacterial growth can be extremely effectively suppressed.

When the hole diameter of the through-hole 62 is set in the range of 1 to 20 μm, it can exhibit a barrier function that prevents passage of human cells, which is inferior to that of conventional barrier membranes, The function of allowing the passage of physiologically active substances that control differentiation, nutrients, gas components, etc. (referred to as elemental components for convenience) can be significantly improved.

Furthermore, if the hole diameter of the through hole is set in the range of 1 to 10 μm, a nearly complete cell barrier can be achieved, and good nutrient component permeability can be obtained. FIG. 6 schematically shows the operation of the perforated plate 60 in which a large number of through holes 62 having a pore diameter within the above range (for example, φ2 μm) are formed in the thin plate-like substrate 61. As shown in the figure, the cell 70 in contact with the perforated plate 60 cannot move through the through-hole 62 having a smaller diameter than itself. On the other hand, elemental components 72 such as physiologically active substances, nutrients, and gas components can move freely through the through holes 62.

By enclosing organ- or tissue-derived cells with such a perforated plate and adjoining the vascular circulatory system, the encapsulated cells are functionally linked to the blood circulatory system inside the living body and perform nutrients, cytokines and gas exchange It can also function as a so-called artificial organ / tissue. Furthermore, it is possible to secure a place for a regenerating organ by space making in a living body, and to incorporate an artificial organ or tissue therein.

In the simple filter model as described above, when the hole diameter of the through hole 62 is larger than that of the cell, it is considered that the cell mass flows out through the through hole. However, according to experiments using periodontal ligament-derived cells, for example, in a porous plate having a pore diameter of 20 μm, a large number of cells adhered to the plate surface and actively spread and proliferated. The through-hole 62 was used exclusively as an anchor for supporting the cell body, and almost no cells penetrated into and penetrated the through-hole 62. In other words, even though the hole diameter of the through-hole 62 is large enough to allow individual cells to pass through, it actually acts as an anchor for the cell and substantially acts as a cell barrier.

Also, the cells adhering to the perforated plate are fixed by hooking the false feet of the cell body at the entrance (hole edge) of the through-hole 62 like a hanging ring. This means that the smaller the formation pitch of the through holes 62, the easier the cells adhere. Therefore, until the distance between the centers of the through holes 62 is about 100 μm, the cells somehow extend the cell bodies into the two adjacent through

holes

62 and 62 as anchors. However, when the distance between the holes exceeds 200 μm, the through holes 62 No longer becomes an anchor, and the cell attachment effect is significantly reduced. Therefore, the distance between the centers of the through holes 62 is preferably 100 μm or less, more preferably 50 μm or less, and still more preferably 30 μm or less. This is because the cell adhesion effect is clearly recognized when the center-to-center distance is 50 μm or less, and the cell adhesion effect is remarkably increased at 30 μm or less.

In the perforated plate 60 of the present invention, the through-hole forming part 63 cut out and used in an appropriate shape at the time of performing tissue regenerative medicine has the through-hole forming cells 66 surrounded by the crosspieces 65 in the surface direction of the plurality of base materials 61. It is spread and formed. In other words, a large number of through holes 62 formed in the through hole forming portion 63 are formed with high density in units of through hole forming cells, and the through holes 62 are separated by the crosspieces 65 between adjacent through hole forming cells. It is in a state.

For this reason, in the perforated plate in which the through holes 62 are formed at a high density without providing the crosspieces 65 in the through hole forming portion 63, the perforated plate is cut out from the through hole forming portion 63 to an appropriate size according to the treatment area (for convenience). However, in the perforated plate 60 of this configuration, the crosspieces 65 may cause the through holes 62 to be bent along the arrangement direction of the through holes 62. As the arrangement is divided, a certain elasticity is maintained and bending of the separator is suppressed. In addition, the presence of the crosspiece 65 prevents the progress of cracks and tearing in the arrangement direction of the through-holes, which are the beginning of the fracture of the material when the plate is bent, and improves the durability against bending of the material. it can. Furthermore, by fixing the shape setting wire frame or the like using the crosspiece 65, it is possible to improve the shapeability of the separation piece while preventing the occurrence of cracks accompanying embrittlement of the through-hole forming cell 66. Become.

Here, the size of the through-hole forming portion 63, the size of each through-hole forming cell 66 (the size of the region bordered by the frame portion 64), the width of the crosspiece 65, and the like are the tissue regeneration performed using this porous plate. It can be set as appropriate according to the medical site and the size of the affected area.

For example, when used as a barrier membrane of the GTR method described above, the size of the through-hole forming portion 63 is about 10 to 40 mm on one side, and the size of the through-hole forming cell 66 is the diameter of a circle inscribed in the cell. It is set to about 0.5 to 5 mm. The width of the crosspiece 65 that borders the through-hole forming cell 66 is set to about 0.1 to 0.5 mm.

By setting the size of the through-hole forming cell 66 so that the diameter of a circle inscribed in the cell is 0.5 to 5 mm (more preferably about 0.8 to 2 mm), the through-hole forming portion 63 is formed. When the cutting piece is cut out to an appropriate size according to the treatment area, a large number of crosspieces 65 coexist with the through-hole forming cell 66 having a sufficient number of through-holes 62 for tissue regenerative medicine as a whole isolation piece. be able to. For this reason, even if bending or cracking or the like occurs during the molding of the separator, the expansion can be suppressed to a minute range of 0.5 to 5 mm. As a result, it is possible to provide a perforated plate that is highly resistant to damage and has good usability. In addition, by setting the width of the crosspiece portion to 0.1 to 0.5 mm, it is possible to give the separation piece appropriate elasticity, and a fixing pin is placed on the crosspiece portion 65 to ensure the separation piece. Can be fixed to.

Further, in the perforated plate 60, the shape of the through-hole forming cells 66 surrounded by the crosspieces 65 is a regular hexagon, and the through-hole forming portions 63 are formed in a honeycomb arrangement pattern. For this reason, not only can bending in a fixed direction along the arrangement of the through-holes 62 and the development of cracks be suppressed, but also uniform bending with respect to any direction acting when the separating piece is deformed into a desired shape. It can have elasticity.

In addition, although the configuration in which the shape of the through-hole forming cell 66 is a regular hexagon is illustrated, among the three pairs of opposite sides facing each other in parallel, the length of one set of opposite sides is longer than the length of the other two sets of opposite sides. Long hexagons may be arranged in a honeycomb shape (arranged without gaps as in the case of regular hexagons). Further, the size of the through-hole forming cell 66, the width of the crosspiece 65, the size and arrangement (formation density) of the through-hole 62 formed in each through-hole forming cell 66 are to be reproduced using the porous plate 60. It can be set to a suitable value depending on the tissue or part to be performed.

In the above, the case where the shape of the through hole 62 in a plan view when viewed from the upper surface side (or the lower surface side) of the base material 61 is circular has been described, but the through hole may have other shapes. For example, as another example of the shape of the through hole, as shown in FIGS. 7A to 7D, (a) a triangular through hole 62a, (b) a rectangular through hole 62b, and (c) a hexagonal through hole 62c, (d) A through hole having an arbitrary shape such as a star-shaped through hole 62d can be formed. In cell tissue regeneration, when the effect of the shape of the through-hole is recognized, the shape can be optimized. In the case of such a through hole, the size of the through hole is set so that the hole diameter when converted to a circular hole is 1 to 50 μm as described above. In the case of the through holes 62a to 62d as described above, the hole diameter converted into a circular hole can be defined as the diameter of a circle inscribed in each shape.

In addition to the through holes (referred to as first through holes) 62, 62a to 62d described above, the hole diameter converted to a circular hole is 80 to 220 μm, as shown in FIG. It is also a preferable form that the second through holes 67 having the same degree are dispersed and formed in the through hole forming cells 66 at a center distance of 2 to 4 mm. The second through-hole 67 is used to guide the blood vessel through the perforated plate. The second through-hole 67 is a blood vessel, that is, an arteriole that is present before becoming a capillary vessel and supplying nutrients to the local tissue. It is for letting go through.

Since the diameter of the arteriole is about 100 to 200 μm, the arteriole can be induced by setting the diameter of the second through hole to 80 to 220 μm (for example, 200 μm), thereby forming a nutrient supply channel by blood flow. I can expect. Further, by forming the formation pitch of the second through holes 67 to 2 to 4 mm (for example, 3 mm), the cell barrier function of the porous plate mainly composed of the first through holes is not impaired, and the porous plate is necessary. It is possible to avoid adhesion with the tissue.

Further, for example, a porous plate in which the hole diameter of the through-hole 62 changes stepwise from the central part to the peripheral part of the through-hole forming cell 66, or a porous plate in which the formation density of the through-holes 62 differs between the central part and the peripheral part It is also possible to provide a perforated plate having an appropriate form depending on the treatment site, the fixing method to the surrounding tissue, etc., such as a perforated plate having a different hole diameter for each through hole forming cell 66. For example, the through-hole forming cell 66 in the region of the central portion 60% of the through-hole forming portion 63 forms a through-hole having a hole diameter of 1 μm with a center-to-center distance of 2 μm, and the through-hole forming cell 66 in the surrounding 25% region is A through hole having a hole diameter of 2 μm is formed with a center-to-center distance of 5 μm, and a through-hole forming cell 66 in a 15% region around the hole is formed with a through hole having a hole diameter of 5 μm with a center-to-center distance of 10 μm. The height and arrangement can be arbitrarily set.

In the above, the configuration in which the shape of the through-hole forming cell 66 surrounded by the crosspiece portion 65 is a hexagon having opposite sides parallel to each other and illustrated in the honeycomb shape in the through-hole forming portion 63 is exemplified. However, the shape and arrangement pattern of the through-hole forming cells 66 can be changed as appropriate.

9 (a) to 9 (d) show other configuration examples of the through hole forming portion 63. FIG. FIG. 9A shows a configuration example in which the shape of the through-hole forming cell 66a is an equilateral triangle, and the bottoms and vertices of the adjacent through-

hole forming cells

66a and 66a are arranged to face each other. FIG. 9B shows a configuration example in which the shape of the through-hole forming cell 66b is a right triangle, and the adjacent through-

hole forming cells

66b and 66b are arranged facing each other on the corresponding sides. FIG. 9C shows a configuration example in which the through-hole forming cell 66c has a square shape and a plurality of through-

hole forming cells

66c, 66c,. FIG. 9D shows a configuration example in which the through-hole forming cell 66d has a square shape and a plurality of through-

hole forming cells

66d, 66d,. FIG. 9 (e) shows a configuration example in which the through-hole forming cell 66e has a rhombus shape and a plurality of through-

hole forming cells

66e, 66e,. FIG. 9F shows a configuration example in which the shape of the through-hole forming cell 66f is a trapezoid and the upper sides and the lower sides of the adjacent through-

hole forming cells

66f and 66f are arranged to face each other.

9A to 9F, in each through hole forming cell, the hole diameter converted to a circular hole is 1 to 50 μm, and the distance between the centers of the adjacent through

holes

62 and 62 is 2. A large number of through holes 62 are formed in a range of ˜200 μm.

Even in the perforated plate having the configuration illustrated in each of the drawings, the arrangement of the through holes 62 is divided by the crosspieces 65 formed between the through hole forming cells, and a certain elasticity is maintained, and is cut out from the through hole forming part. Bending of the separated separator is suppressed. Further, the presence of the crosspiece 65 prevents the progress of cracking and tearing, and the durability against bending of the material can be improved. As can be seen with reference to FIGS. 9A to 9F, the shape and arrangement pattern of the through-hole forming cells 66 can be set as appropriate. For example, a pentagon or more polygon can be combined, and the shape of the through hole forming cell illustrated in FIGS. 9C and 9D can be changed to an arbitrary rectangle such as a rectangle or a parallelogram. good. Further, for example, a regular pentagon and a regular hexagon may be combined to form a soccer ball-like array pattern, and may be configured in combination with through-hole forming cells having different shapes. The shape of the through-hole forming cell may be circular or elliptical. It may be configured with an appropriate arrangement pattern.

FIG. 10 shows a configuration example in which the third through holes 68 for fixing pin placement are formed dispersed in the crosspieces 65. This configuration example exemplifies a configuration in which third through holes 68 having a hole diameter of 0.1 to 0.3 mm are dispersed and formed in the crosspieces 65 with a center distance of 2 to 4 mm. In this configuration example, the hole diameter is fixed to every other apex portion of the through-

hole forming cells

66, 66, 66... Connected in the left-right direction in the crosspiece 65 that borders the regular hexagonal through-hole forming cell 66. A third through hole 68 for pin placement is formed. In addition, a third through hole 68 for placing a fixed pin having the above hole diameter is formed at every other apex portion of the through

hole forming cells

66, 66, 66. Yes. At this time, the third through-holes 68 are arranged at equal intervals in the front-rear and left-right directions. Thereby, the perforated plate which improved the convenience at the time of driving and fixing a fixing pin to the isolation piece cut out from the through-hole formation part 63 can be provided.

Next, a more specific configuration example of the perforated plate produced by the production method of the present invention will be described. FIG. 11 is an external view (entire observation image) of a sample of the porous plate 60A produced by the production method of the present invention. FIG. 12 is a partially enlarged view (enlarged observation image) of the through-hole forming portion 63 in the porous plate 60A shown in FIG. FIG. 13 is a partial enlarged view (transmission enlarged observation image) showing a formation state of the through hole 62 formed in the through hole forming cell 66 of the through hole forming portion 63 shown in FIG.

This perforated plate 60A has a plurality of regular hexagonal through-holes formed in a through-hole forming part 63 of a base material 61 of titanium (medical titanium) having a thickness of 20 μm, with an opposite side distance of 1 mm and a crosspiece 65 having a width of 200 μm. The hole forming cells 66 are distributed in a honeycomb shape. Each through-hole forming cell 66 has a large number of through-holes 62 having a center-to-center distance (formation pitch) in the front-rear and left-right directions of 50 μm and an effective opening diameter of 20 μm.

In addition, the through-hole formed by laser processing generally has a smaller opening diameter on the lower surface of the base material through which the laser light passes than the opening diameter of the upper surface of the base material 61 irradiated with the laser light. For this reason, the inventors observe the through-hole forming portion 63 with a transmission light microscope and set the opening diameter measured from the transmitted light image (that is, the minimum of the through-hole 62) as the effective opening diameter. The effective opening diameter was about 20 μm ± 5 μm.

12, the width of the crosspiece 65 extending in the front-rear direction (vertical direction in FIG. 12) is about 180 μm, and the width of the crosspiece 65 extending obliquely in the left-right direction is about It was 240 μm. This difference is due to the fact that the through holes 62 formed in the through hole forming cell 66 are formed in a lattice shape at equal pitches in the front-rear and left-right directions.

FIG. 14 shows another configuration example (enlarged observation image) of the through hole forming portion 63 in the porous plate 60A shown in FIG. 11, and FIG. 15 shows a partially enlarged view (transmission enlarged observation image). As can be understood by comparing FIGS. 12 and 14 and FIGS. 13 and 15, in the configuration example described above, the through holes 62 are formed at lattice points of a square lattice (square corners each having a side of 50 μm). On the other hand, in this configuration example, the through holes 62 are formed at the lattice points of the triangular lattice (the corners of a regular triangle having a side of 50 μm). The shape and size of the through-hole forming cell 66 are the same as those in the above-described configuration example.

According to such a configuration, since the through holes 62 are arranged along each side of the regular hexagonal through hole forming cell 66, the crosspiece width can be made uniform regardless of the extending direction or position of the crosspiece 65. Yes (see partial enlarged view in FIG. 5). Further, since the hole density per unit area is increased, the number of through holes 62 formed in one through hole forming cell 66 is increased, and the opening area of the through holes in the through hole forming cell 66 is a square lattice shape. There is an increase of about 10% over the sequence.

Next, as another configuration example, a perforated plate in which square through-hole forming cells 66 are formed uniformly (isotropically) is shown in FIGS. Among these, FIG. 16 is a sample image of a perforated plate 60B in which square through-hole forming cells 66 are formed in a square lattice shape, (a) is an external view (overall observation image), and (b) is a through-hole forming portion 63. It is a partial enlarged view (enlarged observation image). Similarly, FIG. 17 is a sample image of a perforated plate 60C in which square through-hole forming cells 66 are formed in a staggered pattern, where (a) is an external view, and (b) is a partially enlarged view of a through-hole forming portion 63. It is.

In the

perforated plates

60B and 60C, a plurality of square through-hole forming cells 66 having an opposite side distance of 1 mm and a crosspiece 65 having a width of 200 μm are uniformly formed in a through-hole forming portion 63 of a titanium base 61 having a thickness of 20 μm. A distribution is formed. Each through-hole forming cell 66 is formed with a large number of through-holes 62 having a center-to-center distance (formation pitch) of 50 μm in the front-rear and left-right directions and an effective opening diameter of 20 μm, similarly to the porous plate 60A described above. The measured effective aperture diameter was about 20 μm ± 5 μm, and the width of the crosspiece was about 180 μm in both the front and rear and left and right directions.

As still another configuration example, FIG. 18 shows a partial enlarged observation image of a perforated plate 60D in which small-diameter through holes are formed at a higher density than the configuration examples shown in FIGS. In the perforated plate 60D, the base material 61 is made of titanium, and the plate thickness is 20 μm. The through hole 62 formed in the substrate 61 has a hole diameter of 1 μm, and the distance between the centers of adjacent through holes is 3 μm. From this image, it can be seen that fine through-holes 62 having a hole diameter of only 1 μm are uniformly and densely formed with a fine formation pitch of 3 μm. It is also understood that even when the through holes 62 are formed at such a high density, the flatness before the hole processing is maintained without the base material 61 being distorted or bent by thermal stress. .

Next, hole processing is performed by changing the conditions of the laser beam irradiated to the workpiece (perforated plate substrate), and the heat affected zone (HAZ: also called heat affected zone) is investigated. A table of the experimental results is shown in FIG. The conditions of the workpiece and the conditions of the through holes are the same, both of which are made of titanium (medical pure titanium), the plate thickness is 20 μm, and the diameter of the formed through holes is 15 μm. The `` heat-affected region '' used in the description of the present embodiment refers to a region where a change such as discoloration is observed by visually observing the workpiece with the through hole formed with a microscope, and each numerical value is The thickness of the heat affected area (width of the annular change area) measured in the microscope field is shown.

Example 1 is an experimental result when the conditions of the laser beam irradiated to the workpiece are set to wavelength λ = 1028 nm, average power P = 300 mW, and pulse width Wp = 300 fsec (femtosecond). At this time, the thickness of the observed heat-affected region was significantly smaller than 1 μm.

Example 2 is an experimental result when the conditions of the laser beam applied to the workpiece are set to wavelength λ = 532 nm, average power P = 500 mW, and pulse width Wp = 500 psec (picoseconds). At this time, the observed thickness of the heat affected zone was about 1 μm.

Example 3 is an experimental result when the conditions of the laser beam applied to the workpiece are set to a wavelength λ = 1060 nm, an average power P = 800 mW, and a pulse width Wp = 5 nse. At this time, the observed thickness of the heat affected zone was about 2 μm.

Comparative Example 1 is an experimental result when the conditions of the laser beam applied to the workpiece are set to wavelength λ = 532 nm, average power P = 2 W, and pulse width Wp = 40 nsec. At this time, the thickness of the observed heat-affected region was about 6 μm.

From this experimental result, it can be seen that the thickness of the heat-affected region increases as the pulse width of the laser beam applied to the workpiece increases. It can also be seen that by defining the pulse width of the laser light, the thickness of the heat-affected region can be suppressed to a desired range even if the wavelength and average power of the laser light are somewhat different. This is because the absorption coefficient of the laser beam in the substrate does not change greatly in the wavelength range of the laser beam in which the above experiment was performed, and the thermal diffusion distance does not change depending on the power of the irradiated laser beam. .

FIG. 20 and FIG. 21 are enlarged micrographs of the experimental results of cell adhesion to a titanium porous plate. FIG. 20 shows the experimental results of cell attachment to a perforated plate having through holes with a diameter of 20 μm and a formation pitch of 30 μm. In the figure, a large number of cell attachments are seen around the through-holes that appear dark circles. On the other hand, FIG. 21 is a comparative example different from the present invention, and shows the results of cell attachment to a perforated plate having a minimum through-hole diameter of 200 μm and a formation pitch of 300 μm. In the figure, only a small amount of cell attachment is seen around the through-hole that appears to be a bright circle, and no cell attachment is seen on the surface matrix portion. As described above, it was shown that the plate of the present invention has an excellent cell adhesion ability.

LS Laser processing system 10 Laser device 20 Beam scanner 25 fθ lens 30 Stage 50 Control device 60 (60A, 60B, 60C, 60D) Perforated plate 61 Base material 62 (62a to 62d) Through hole 63 Through hole forming portion 64 Frame portion 65 Crosspiece 66 (66a to 66f) Through-hole forming cell 67 Second through-hole 68 Third through-hole 70 Cell 72 Element component W such as physiologically active substance, nutrient, gas component W Work material

Claims

A medical porous plate provided with a through-hole forming portion in which a plurality of through-holes are formed and a frame portion surrounding the through-hole forming portion on a thin plate-like base material,
The through-hole forming portion includes a crosspiece that is connected to the frame portion and extends in the front-rear and left-right directions to partition the through-hole formation portion into a plurality of pieces, and a plurality of through-hole forming cells surrounded by the crosspiece. ,
The through-hole formed in the through-hole forming cell has a hole diameter converted to a circular hole of 1 to 50 μm, and a distance between centers of adjacent through holes is 2 to 200 μm. plate.
2. The medical porous plate according to claim 1, wherein the base material is a biocompatible metal material having a thickness of 2 to 100 μm.
3. The medical porous plate according to claim 1, wherein the through hole forming cell surrounded by the crosspiece has a diameter of a circle inscribed in the cell of 0.5 to 5 mm. .
The medical porous plate according to any one of claims 1 to 3, wherein the crosspiece has a width of 0.1 to 0.5 mm.
The second through hole having a hole diameter converted to a circular hole of 80 to 220 μm in addition to the through hole is formed by being dispersed in the through hole forming cell at a center distance of 2 to 4 mm. The medical porous plate according to any one of 1 to 4.
The shape of the through-hole forming cell surrounded by the crosspiece is a regular polygon, and the through-hole forming cells are uniformly distributed in the through-hole forming portion. The medical porous plate according to any one of 5.
The shape of the through-hole forming cells surrounded by the crosspieces is a hexagon with opposite sides parallel to each other, and the through-hole forming cells are distributed and formed in the through-hole forming portion in a honeycomb shape. The medical porous plate according to any one of claims 1 to 5.
A method for producing a porous plate for medical use in which a thin plate-like substrate is irradiated with laser light to form a plurality of through holes in a through hole forming portion surrounded by a frame portion,
A laser beam having a pulse width determined based on a thermal diffusion distance in the base material is left in the through hole forming portion, leaving a crosspiece that extends to the front, rear, left, and right connected to the frame portion and divides the through hole forming portion into a plurality of portions. Irradiated,
A through hole having a hole diameter converted to a circular hole of 1 to 50 μm and a distance between centers of adjacent through holes of 2 to 200 μm is formed,
A method for manufacturing a porous plate for medical use, wherein a plurality of through-hole forming cells each having a plurality of through-holes formed therein are formed in the through-hole forming portion.
The method for producing a porous plate for medical use according to claim 8, wherein the substrate is a biocompatible metal material having a plate thickness of 2 to 100 µm.
The method for manufacturing a medical porous plate according to claim 8 or 9, wherein the thermal diffusion distance is 1 µm or less.
The method for producing a porous plate for medical use according to any one of claims 8 to 10, wherein the pulse width is 10 nsec or less.
Fabrication of a porous plate for medical use in which a thin plate-like substrate made of titanium or titanium alloy having a thickness of 2 to 100 μm is irradiated with laser light to form a plurality of through holes in the through hole forming portion surrounded by the frame portion A method,
In the through-hole forming part, leaving a beam part connected to the frame part and extending in the front-rear and left-right directions, and dividing the through-hole forming part into a plurality of parts, irradiating with a laser beam having a pulse width of 10 nsec or less,
A through hole having a hole diameter converted to a circular hole of 1 to 50 μm and a distance between centers of adjacent through holes of 2 to 200 μm is formed,
A method for manufacturing a porous plate for medical use, wherein a plurality of through-hole forming cells each having a plurality of through-holes formed therein are formed in the through-hole forming portion.
The size of the through hole forming cell surrounded by the crosspiece is such that a diameter of a circle inscribed in the cell is 0.5 to 5 mm. Manufacturing method for medical porous plate.
The method for producing a porous plate for medical use according to any one of claims 8 to 13, wherein a width of the crosspiece is 0.1 to 0.5 mm.
9. The second through hole having a diameter of 80 to 220 μm converted to a circular hole in addition to the through hole is formed by being dispersed in the through hole forming cell at a center distance of 2 to 4 mm. The method for producing a medical porous plate according to any one of 1 to 14.
The shape of the through-hole forming cells surrounded by the crosspieces is a regular polygon, and the through-hole forming cells are uniformly distributed in the through-hole forming portions. The method for producing a porous plate for medical use according to any one of 15.
The shape of the through-hole forming cells surrounded by the crosspieces is a hexagon with opposite sides parallel to each other, and the through-hole forming cells are distributed and formed in the through-hole forming portion in a honeycomb shape. The method for producing a porous plate for medical use according to any one of claims 8 to 15.